Laverty Pathology

Sydney, Australia

Laverty Pathology

Sydney, Australia
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Pusceddu I.,Saarland University | Farrell C.-J.L.,Laverty Pathology | Di Pierro A.M.,District Hospital of Bolzano | Jani E.,District Hospital of Bolzano | And 3 more authors.
Clinical Chemistry and Laboratory Medicine | Year: 2015

Aging is a complex biological process characterized by a progressive decline of organ functions leading to an increased risk of age-associated diseases and death. Decades of intensive research have identified a range of molecular and biochemical pathways contributing to aging. However, many aspects regarding the regulation and interplay of these pathways are insufficiently understood. Telomere dysfunction and genomic instability appear to be of critical importance for aging at a cellular level. For example, age-related diseases and premature aging syndromes are frequently associated with telomere shortening. Telomeres are repetitive nucleotide sequences that together with the associated sheltrin complex protect the ends of chromosomes and maintain genomic stability. Recent studies suggest that micronutrients, such as vitamin D, folate and vitamin B12, are involved in telomere biology and cellular aging. In particular, vitamin D is important for a range of vital cellular processes including cellular differentiation, proliferation and apoptosis. As a result of the multiple functions of vitamin D it has been speculated that vitamin D might play a role in telomere biology and genomic stability. Here we review existing knowledge about the link between telomere biology and cellular aging with a focus on the role of vitamin D. We searched the literature up to November 2014 for human studies, animal models and in vitro experiments that addressed this topic.


Bowditch R.C.,Laverty Pathology | Clarke J.M.,Laverty Pathology | Baird P.J.,Laverty Pathology | Greenberg M.L.,Laverty Pathology
Diagnostic Cytopathology | Year: 2012

BD FocalPoint GS™ computer-assisted screening of BD SurePath® liquid-based cervical cytology slides (SP + FP) was compared with screening an accompanying conventional cervical Papanicolaou (Pap) smear (CON) in a split sample trial of 2,198 routine specimens. The rate of unsatisfactory specimens in the SP + FP arm was 0.2% compared with 4.1% in the conventional Pap smear, a significant reduction. There was no statistically significant difference between SP + FP and CON for the detection of histologically confirmed high-grade (HG) lesions in the routine split sample specimens (n = 9). To further test the sensitivity of SP + FP for HG lesions, 38 SurePath slides from confirmed HG cases, without an accompanying CON, were interpolated among the routine smears. In every one of the 47 confirmed HG cases, either HG cells were present in the microscope fields selected by FocalPointGS™ for review by the screening cytologist (46 of 47), or full screening of the slide was indicated by the FocalPointGS™ (1 of 47), confirming the effectiveness of SP + FP technology for primary screening. In a small number of cases, the screening cytologist did not recognize the abnormality even though on review HG cells were present in fields selected by FocalPointGS™. The overall detection rate was 93% for HG squamous lesions; 89% for known HG endocervical glandular lesions; and 91% for known endometrial carcinoma. In conclusion, the SP + FP detected 100% of HG abnormalities in the trial set; significantly reduced the rate of unsatisfactory specimens; and improved the overall screening rate of detection of HG abnormalities particularly of glandular lesions when compared with other screening technologies. Copyright © 2011 Wiley Periodicals, Inc.


Farrell C.-J.L.,Laverty Pathology | Carter A.C.,Laverty Pathology
Annals of Clinical Biochemistry | Year: 2016

Clinical laboratories frequently encounter samples showing significant haemolysis, icterus or lipaemia. Technical advances, utilizing spectrophotometric measurements on automated chemistry analysers, allow rapid and accurate identification of such samples. However, accurate quantification of haemolysis, icterus and lipaemia interference is of limited value if laboratories do not set rational alert limits, based on sound interference testing experiments. Furthermore, in the context of increasing consolidation of laboratories and the formation of laboratory networks, there is an increasing requirement for harmonization of the handling of haemolysis, icterus and lipaemia-affected samples across different analytical platforms. Harmonization may be best achieved by considering both the analytical aspects of index measurement and the possible variations in the effects of haemolysis, icterus and lipaemia interferences on assays from different manufacturers. Initial verification studies, followed up with ongoing quality control testing, can help a laboratory ensure the accuracy of haemolysis, icterus and lipaemia index results, as well as assist in managing any biases in index results from analysers from different manufacturers. Similarities, and variations, in the effect of haemolysis, icterus and lipaemia interference in assays from different manufacturers can often be predicted from the mechanism of interference. Nevertheless, interference testing is required to confirm expected similarities or to quantify differences. It is important that laboratories are familiar with a number of interference testing protocols and the particular strengths and weaknesses of each. A rigorous approach to all aspects of haemolysis, icterus and lipaemia interference testing allows the analytical progress in index measurement to be translated into improved patient care. © 2016, © The Author(s) 2016.


Farrell C.-J.,Laverty Pathology | Herrmann M.,District Hospital of Bolzano
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2013

The demand for analysis of 25-hydroxyvitamin D has increased dramatically throughout the world over the past decade. As a consequence, a number of new automated assays have been introduced for 25-hydroxyvitamin D measurement. Automated assays have shown variable ability to meet the technical challenges associated with 25-hydroxyvitamin D measurement. Assays are able to meet performance goals for precision at high concentrations but fail to do so at low concentrations of 25-hydroxyvitamin D. The overall accuracy of automated methods has improved over recent years and generally shows good overall agreement with reference methods; however, discrepancies persist for individual samples. Liquid chromatography-tandem mass spectrometry is used by some routine laboratories for 25-hydroxyvitamin D analysis but its widespread use is hampered by limited sample throughput. 1,25-Dihydroxyvitamin D is an important analyte in specific clinical situations, which remains in the hands of specialised laboratories using manual analytical methods. © 2013 Elsevier Ltd. All rights reserved.


Kvannli L.,The Surgical Center | Benger R.,The Surgical Center | Benger R.,Macquarie University | Benger R.,Sydney Eye Hospital | And 2 more authors.
Orbit | Year: 2012

Background: The senior consultants Ross Benger and Andrew Gal have been using en face frozen section histological margin control in removing cancer from the periocular region since 1985. The aim of this study was to determine the percentage of cases in which more than one resection was necessary in order to achieve clear margins. Methods: This is a retrospective study of patients treated at Drummoyne Eye Surgical Centre in the period 1999-2007, in whom removal of the eyelid cancer was decided to be with en face frozen section histological control. A record was kept of how many resections were necessary to achieve clear margins. Paraffin sections were subsequently examined for a final histopathological diagnosis. Results: Two hundred and fifty people were included in the study, of whom 204 had basal cell carcinoma (BCC) and 32 had squamous cell carcinoma (SCC). One hundred and twenty BCCs had a full-thickness eyelid "wedge" resection, of which 45% needed more than the standard two frozen sections taken to achieve clear margins. Eighty-four BCCs were removed using ring resection, of which 35.7% needed more than the standard initial resections (peripheral annulus and deep disc) to achieve clear margins. Conclusions: Our study showed that a significant percentage of BCC and SCC lesions needed further resection after the initial frozen section edge checks to achieve clear margins. Intraoperative presence of the histopathologist increased the likelihood of achieving clearance of the cancer at a single operating session. © 2012 Informa Healthcare USA, Inc.


Farrell C.-J.L.,Laverty Pathology | Kirsch S.H.,Saarland University | Herrmann M.,District Hospital of Bolzano
Clinical Chemistry and Laboratory Medicine | Year: 2013

Folate deficiency has been linked to diverse clinical manifestations and despite the importance of accurate assessment of folate status, the best test for routine use is uncertain. Both serum and red cell folate assays are widely available in clinical laboratories; however, red cell folate is the more time-consuming and costly test. This review sought to evaluate whether the red cell assay demonstrated superior performance characteristics to justify these disadvantages. Red cell folate, but not serum folate, measurements demonstrated analytical variation due to sample pre-treatment parameters, oxygen saturation of haemoglobin and haematocrit. Neither marker was clearly superior in characterising deficiency but serum folate more frequently showed the higher correlation with homocysteine, a sensitive marker of deficiency. Similarly, both serum and red cell folate were shown to increase in response to folic acid supplementation. However, serum folate generally gave the greater response and was able to distinguish different supplementation doses. The C677T polymorphism of methylenetetrahydrofolate reductase alters the distribution of folate forms in red cells and may thereby cause further analytical variability in routine red cell folate assays. Overall, serum folate is cheaper and faster to perform than red cell folate, is influenced by fewer analytical variables and provides an assessment of folate status that may be superior to red cell folate.


Farrell C.,Laverty Pathology | Soldo J.,DiaSorin Inc. | Williams P.,University of Sydney | Williams P.,Royal Prince Alfred Hospital | And 3 more authors.
Clinical Chemistry and Laboratory Medicine | Year: 2012

Background : Clinical laboratories require accurate and precise 25-hydroxyvitamin D (25-OHD) immunoassays to allow comparison of patient results with published decision limits. However, some variation in performance has been found with the previous generation of automated 25-OHD immunoassays. This study assessed the performance of four recently released automated 25-OHD immunoassays against a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. Methods : A total of 983 samples from apparently healthy adults, plus 253 samples chosen to challenge the performance of the assays, were analyzed by the latest generation of immunoassays from Abbott, DiaSorin, Roche and Siemens. LC-MS/MS analysis was performed on a random subset of 264 samples. The precision of the immunoassays was assessed over 5 days with samples ranging between 3.0 and 370 nmol/L in concentration. Results : Immunoassays showed significant differences in precision at 25-OHD concentrations of 3.0 - 86.5 nmol/L but all showed acceptable precision at higher concentrations. The DiaSorin assay agreed with LC-MS/MS across the measuring range of samples tested (7.7 - 425 nmol/L). The other assays showed generally good performance, but had some limitations when their performance was challenged with samples with low and high 25-OHD concentrations, heterophilic antibodies or high 25-OHD 2 concentrations. The C3-epimer of 25-OHD was identified in 40.4 % of healthy adults tested and was a source of analytical variance in immunoassays. Conclusions : The latest generation of 25-OHD immunoassays has improved performance compared to previous assays. However, some immunoassays can still give discrepant results and this is most apparent when immunoassays are evaluated with a range of samples that challenge their analytical performance. © 2012 by Walter de Gruyter Berlin Boston.


Farrell C.-J.L.,Laverty Pathology | Soldo J.,DiaSorin Inc. | McWhinney B.,Pathology Queensland | Bandodkar S.,Laverty Pathology | And 4 more authors.
Clinical Chemistry and Laboratory Medicine | Year: 2014

Methods: 25-OHD was measured in 1236 samples using automated assays from Abbott, DiaSorin, Roche and Siemens. A subset of 362 samples had up to three liquid chromatography-tandem mass spectrometry 25-OHD analyses performed. 25-OHD2 recovery, dilution recovery, human anti-animal antibody (HAAA) interference, 3-epi-25-OHD3 cross-reactivity and precision of the automated assays were evaluated.Background: Current automated immunoassays vary significantly in many aspects of their design. This study sought to establish if the theoretical advantages and disadvantages associated with different design formats of automated 25-hydroxyvitamin D (25-OHD) assays are translated into variations in assay performance in practice.Results: The assay that combined release of 25-OHD with analyte capture in a single step showed the most accurate 25-OHD2 recovery and the best dilution recovery. The use of vitamin D binding protein (DBP) as the capture moiety was associated with 25-OHD2 under-recovery, a trend consistent with 3-epi-25-OHD3 cross-reactivity and immunity to HAAA interference. Assays using animal-derived antibodies did not show 3-epi-25-OHD3 cross-reactivity but were variably susceptible to HAAA interference. Not combining 25-OHD release and capture in one step and use of biotin-streptavidin interaction for solid phase separation were features of the assays with inferior accuracy for diluted samples. The assays that used a backfill assay format showed the best precision at high concentrations but this design did not guarantee precision at low 25-OHD concentrations.Conclusions: Variations in design among automated 25-OHD assays influence their performance characteristics. Consideration of the details of assay design is therefore important when selecting and validating new assays.


Farrell C.-J.L.,Laverty Pathology | Farrell C.-J.L.,Royal North Shore Hospital | Martin S.,Laverty Pathology | McWhinney B.,Pathology Queensland | And 4 more authors.
Clinical Chemistry | Year: 2012

BACKGROUND: Vitamin D testing is increasing worldwide. Recently several diagnostic manufacturers including Abbott and Siemens have launched automated 25-hydroxy vitaminD(25OH-D) immunoassays. Furthermore, preexisting assays from DiaSorin and Roche have recently been modified. We compared the performance of 5 automated immunoassays, an RIA and 2 liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. METHODS: Aliquots of 170 randomly selected patient samples were prepared and 25OH-D was measured by 2 LC-MS/MS methods, an RIA (DiaSorin), and automated immunoassays from Abbott (Architect), DiaSorin (LIAISON), IDS (ISYS), Roche (E170, monoclonal 25OH-D 3 assay), and Siemens (Centaur). Within-run and between-run imprecision were evaluated by measurement of 5 replicates of 2 serum pools on 5 consecutive days. RESULTS: The LC-MS/MS methods agreed, with a concordance correlation coefficient (CCC) of 0.99 and bias of 0.56 μg/L (1.4 nmol/L). The RIA assay showed a performance comparable to LC-MS/MS, with aCCCof 0.97 and a mean bias of 1.1 μg/L (2.7 nmo/L). All immunoassays measured total 25OH-D (including D 3and D 2), with the exception of the Roche assay (D 3only). Among the immunoassays detecting total 25OH-D, the CCCs varied between 0.85 (Abbott) to 0.95 (LIAISON). The mean bias ranged between 0.2 μg/L (0.5 nmol/L) (LIAISON) and 4.56 μg/L (11.4 nmol/L) (Abbott). The Roche 25OH-D 3 assay demonstrated small mean bias [-2.7 μg/L (-6.7 nmol/L)] [-2.7 μg/L (-6.7 nmol/L)] but a low CCC of just 0.66. Most assays demonstrated good intra- and interassay precision, with CV <10%. CONCLUSIONS: Automated immunoassays demonstrated variable performance and not all tests met our minimum performance goals. It is important that laboratories be aware of the limitations of their assay. © 2011 American Association for Clinical Chemistry.


PubMed | Laverty Pathology
Type: Journal Article | Journal: Annals of clinical biochemistry | Year: 2016

Clinical laboratories frequently encounter samples showing significant haemolysis, icterus or lipaemia. Technical advances, utilizing spectrophotometric measurements on automated chemistry analysers, allow rapid and accurate identification of such samples. However, accurate quantification of haemolysis, icterus and lipaemia interference is of limited value if laboratories do not set rational alert limits, based on sound interference testing experiments. Furthermore, in the context of increasing consolidation of laboratories and the formation of laboratory networks, there is an increasing requirement for harmonization of the handling of haemolysis, icterus and lipaemia-affected samples across different analytical platforms. Harmonization may be best achieved by considering both the analytical aspects of index measurement and the possible variations in the effects of haemolysis, icterus and lipaemia interferences on assays from different manufacturers. Initial verification studies, followed up with ongoing quality control testing, can help a laboratory ensure the accuracy of haemolysis, icterus and lipaemia index results, as well as assist in managing any biases in index results from analysers from different manufacturers. Similarities, and variations, in the effect of haemolysis, icterus and lipaemia interference in assays from different manufacturers can often be predicted from the mechanism of interference. Nevertheless, interference testing is required to confirm expected similarities or to quantify differences. It is important that laboratories are familiar with a number of interference testing protocols and the particular strengths and weaknesses of each. A rigorous approach to all aspects of haemolysis, icterus and lipaemia interference testing allows the analytical progress in index measurement to be translated into improved patient care.

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